Immune dysfunction is common to both the alcoholic and AIDS patient, and one deficiency shared by these two groups is a decrease in natural killer (NK) cell activity that is an important host defense mechanism against certain infections and neoplastic diseases. While some studies show that NK cell activity is decreased by alcohol, other studies have reported no change or even increased NK cell activity. Interpretation of these studies is difficult because NK cell activity can be influenced by nutritional and liver status and the nature of the experimental conditions. The effect of alcohol on NK cell function is unclear. Our preliminary data indicate that chronic high alcohol consumption decreases pooled splenic NK cell activity. Thus, our objective is to confirm our preliminary findings in individual mice and to determine the dose level, and duration of feeding required to induce a decrease in NK cell activity. We will correlate these effects with blood alcohol level in mice chronically fed three dose levels of alcohol and solid diet that maintains nutritional status. We will also assess the effect of alcohol on experimental and spontaneous metastasis of B16-bladder 6 melanoma, a highly invasive and metastatic cell line, to determine the biological significance of alcohol-induced decrease in NK cell activity. Lastly, we will undertake studies to identify the mechanism underlying alcohol's effect on NK cell activity. We will conduct experiments to determine if a) effector target binding is altered, b) suppressor factors are involved in inhibiting NK cell activity, and c) examine whether alcohol decreases the number of NK cells. To do the latter, we will quantify and sort NK cell populations using fluorescence activated cell sorting based on the expression of asialo-GM1 and NK-1 surface markers. In correlating the effect that alcohol has on NK cells with the effects reported in the AIDS patient, our investigation may implicate alcohol as a potential risk for increasing susceptibility to Kaposi's sarcoma and other neoplastic diseases in the AIDS patient and in the alcohol abuser to developing AIDS and cancer.